Interpretive Summary: It is not uncommon in the field of nutrition for the results from observational studies to differ from interventional studies, particularly randomized controlled trials. We hypothesized that this difference is the result of differences in the translational paths of nutrient–disease associations, that is, the timing between identifying a nutrient/disease relationship and appearance of data to support the relationship in the published literature. We assessed translational paths using published literature by comparing the two recent examples, one in which the observational studies and interventional studies yielded similar findings, very long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) and heart disease, and one in which the observational studies and interventional studies yielded different findings, vitamin E and heart disease. We performed systematic review of the literature for each example, constructed citation network by tracking the appearance in the literature of observational, interventional, animal and cell culture studies. We then compared the two topics with respect to the number of articles and citation relationships between them, as well as the distribution of articles among the different categories. For n-3 PUFA, all the data consistently suggested that higher intake was associated with lower heart disease. For vitamin E, the observational studies suggested an inverse association, the higher the vitamin E intake, the lower heart disease; whereas the interventional data indicated no benefit to increasing vitamin E intake. We identified no differences between the translational paths of the two nutrient–disease associations. In the two examples, citation network characteristics do not predict concordance in the results of observational studies and interventional studies.

Technical Abstract:
There are several examples in nutrition of discordance between the results of observational studies and randomized controlled trials (RCTs). We hypothesized that this discordance is attributable to differences in the translational paths of nutrient–disease associations. Translational paths can be assessed using citation analysis. We compared the characteristics of citation networks using examples, where RCTs and observational studies agreed (long-chain n-3 polyunsaturated fatty acids [n-3 PUFA]) or disagreed (vitamin E). We performed systematic reviews in each example, constructed citation networks, and compared them with respect to the number of articles and citation relationships between them, as well as the distribution of articles' hub and authority scores. For n-3 PUFA, meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality. For vitamin E, the meta-analysis of 14 RCTs excluded a clinically significant effect, whereas 14 observational studies reported a significant inverse association. The respective citation networks consisted of 392 (n-3 PUFA) and 351 (vitamin E) articles. No differences between the characteristics of the two networks were identified. There was no evidence that the observational studies predated RCTs in the translational process in either example. In the two examples, citation network characteristics do not predict concordance in the results of observational studies and RCTs.